Inflammatory bowel disease (IBD) refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease. Whereas ulcerative colitis is an inflammatory disease of the large intestine that affects the mucosa of the intestine which becomes inflamed and develops ulcers, Crohn's disease most commonly affects the last part of the small intestine, the terminal ileum, and parts of the large intestine. However, Crohn's disease is not limited to these areas and can occur in any part of the digestive tract. Crohn's disease causes inflammation that extends much deeper into the layers of the intestinal wall than ulcerative colitis does. Crohn's disease generally tends to involve the entire bowel wall, whereas ulcerative colitis affects only the lining of the bowel.
Medical research has not determined yet what causes inflammatory bowel disease. It is however believed that a number of factors may be involved, such as the environment, diet, and possibly genetics. The drug treatment for IBD usually consists of anti-inflammatory drugs and immunosuppressive agents. However, current therapy to control IBD is not always effective, and surgical procedures are still necessary in many cases. Today, about 70 to 80% of patients with Crohn's disease and 30 to 40% with ulcerative colitis ultimately require surgery, indicating the lack of efficiency of the currently used therapeutics.
With respect to intestinal health problems in animals such as dysbacteriosis, currently antibiotics are used as a treatment. Also a wide variety of feed additives are on the market, including essential oils, fatty acid preparations, pre- and probiotics, and combinations of products of which it is claimed that they improve gastrointestinal tract health. Their use however is empirical and their efficacy is not scientifically proven.
Currently butyric acid is used in the treatment of IBD, but the actual delivery of butyric acid into the gastrointestinal tract is problematic. Several mechanisms have already been proposed, including the use of butyrate coated tablets, butyrate enemas or the use of natural fermentation in the gastrointestinal tract using dietary fibre. These currently known approaches show significant drawbacks. When using butyric coated tablets the problem lays in the release of their content at the intended location and because of the inter-individual differences in gastrointestinal tract lumen pH and transit time (Ibekwe et al., 2006; Roda et al. 2007) the release cannot be optimised. Moreover taste of the tablets is very unpleasant. The use of rectal butyric acid enemas on the other hand is hampered by a low compliance rate and a short and discontinuous exposure of the colon mucosa to butyrate (Breuer et al., 1997). When using the fermentation of dietary fibre for butyrate production the use of resistant starch and oligofructose have been associated with a greater butyrate production (Morrison et al 2006). The stimulation of butyrate production however depends on the presence of bacteria expressing butyryl CoA:acetyl CoA transferase and the regional differences in lactate utilising, butyrate producing bacteria (Morrison et al 2006). Therefore, this approach is not uniform and the outcome cannot be predicted. For the treatment of dysbacteriosis in animals at this moment a powder form or coated butyric acid administration to the feed is used. This results however in similar problems as stated above, additionally having a negative sensory aspect that is unfavourable for the animals.
Another approach to deliver butyric acid into the gastrointestinal tract is the administration of butyric acid-producing bacteria, enabling in situ production of butyric acid. In this regard, Sokol et al. (Proc Natl Acad Sci USA, 2008:16731) disclose that the butyrate-producing bacterium Faecalibacterium prausnitzii or culture supernatants of this bacterium are capable in decreasing inflammation and necrosis in rodent IBD models. WO 2004/085628 further discloses that lactic acid-utilizing bacteria which also produce butyric acid, such as the bacterium species Anaerostipes caccae, might be used in a method for treating diseases associated with a high dosage of lactic acid such as IBD.
Eeckhaut et al. 2008 recently described the isolation of butyrate-producing bacterial isolates belonging to the novel species Butyricicoccus pullicaecorum. The latter novel species has as type strain the isolate 25-3T which is deposited at the public BCCM/LMG bacterial collection as B. pullicaecorum LMG24109.
The present invention relates to the unexpected finding that butyrate producing strains related to the species B. pullicaecorum are superior in their capability to prevent or cure intestinal health problems of humans or animals compared to other butyrate-producing species such as Faecalibacterium prausnitzii, Anaerostipes caccae or Anaerostipes butyricus. Hence the present invention relates to the delivery of B. pullicaecorum which is much more effective than comparable delivery methods and further also overcomes all the disadvantages as stated above.
The present invention thus solves the problem of finding more efficient and effective compounds and methods to treat intestinal health problems in humans or animals. The present invention provides new compositions for prophylaxis and/or treatment of intestinal health problems in humans or animals.